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Alport Syndrome in Older Adults: What is the Evidence?
Corresponding author: Henry HL Wu, Department of Renal Research, Kolling Institute of Medical Research, Royal North Shore Hospital & The University of Sydney, Renal Research Laboratory, Sydney, Australia. E-mail: hon.wu@sydney.edu.au
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Received: ,
Accepted: ,
How to cite this article: Shaban A, Li WC, Chinnadurai R, Ponnusamy A, Wu HHL. Alport Syndrome in Older Adults: What is the Evidence? Indian J Nephrol. doi: 10.25259/IJN_820_2025
Dear Editor,
Alport syndrome (AS) is a hereditary nephropathy, with disease onset typically occurring in childhood or early adulthood. Few reports record cases in which AS was first diagnosed later in life (i.e., age ≥50 years). Initial clinical presentations of AS in older adults may be subtle, lack the classical features, and are hence challenging to diagnose clinically. We identified 11 peer-reviewed publications reporting AS where case individuals were first diagnosed at ages ≥50 years [Table 1].S1-S10
| Author(s), year of publication | Study design | Age at diagnosis (years) | Sex | Ethnic origin | Clinical manifestation | Genetic mutation |
|---|---|---|---|---|---|---|
| Khorsan et al.,S1 2025 | Case report | 78 | Male | Not specified | Persistent hematuria, sensorineural hearing loss, hypertension, and kidney cysts | COL4A4 gene (p.Gly408Glu) |
| Rana et al.,S2 2025 | Case report | 66 | Male | Hispanic | Proteinuria and rising creatinine | COL4A4 gene (c.3022G>A:p.Gly1008Arg) |
| Hernandez et al.,S3 2023 | Case report | 62 | Female | Hispanic | Kidney cysts, microscopic hematuria, proteinuria, arthritis, otalgia, and hypertension. | COL4A4 gene (c.2794A>T:p.Lys932) |
| Chen et al.,S4 2023 | Case report | 59 | Female | Chinese | Microscopic hematuria and proteinuria | COL4A3 gene (c.888G>A:p.Gln296Gln) |
| Rahimzadeh et al.,S5 2023 | Case report | 50 | Female | Not specified | Edema, microscopic hematuria, and proteinuria (>1g/day). | Genetic testing was not performed |
| Hoefele et al.,S6 2010 | Case report on a family (3 members) | 13 (son) 46 (father) 70 (paternal grandfather) | Male | Italian | Hematuria and proteinuria. Persistent hematuria and proteinuria. Kidney stones and ESKD (grandfather). | COL4A3 gene (p.G291E in exon 15) |
| Liu and XieS7, 2025 | Case report | 55 | Female | Not specified | Proteinuria, hematuria, and hypertension | COL4A4 gene (c.913G > C:p.Gly305Arg) |
| Daga et al.,S8 2024 | Case report on a family (2 members) | 62 64 (maternal cousin) | Female | Italian | Proteinuria and microscopic hematuria | COL4A3 gene (c.765G>A:p.Thr255Thr) |
| - | 6 male and 2 female | Cypriot | Two females and one male were heterozygous carriers. Five affected males reached ESKD. | COL4A5 gene (P628L mutation) | ||
| - | 8 males and 5 females | Cypriot | Four affected males - two developed ESKD, 2 showed mild kidney impairment. Others had microscopic hematuria | |||
| Wilson et al.,S9 2007 | Case report on a family (8 members) | 32,36,39,39, 41,42,60,64 | Male and female | New Zealand | Two progressed to ESKD Four had CKD, No extrarenal manifestations. | COL4A5 gene (c.4913G>A:p.Cys1638Tyr) |
| Gross et al.,S10 2025 | Single-center observational study | 45 is the mean age at diagnosis, with numerous patients diagnosed at age ≥ 50 | Female 66% Male 34% | Mixed | Females - less severe involvement. Males with X-linked disease and lower eGFR most likely progress. | COL4A5 gene (61.2%) Autosomal dominant (18.2%) Others (20.6%) |
Many had long-standing microscopic hematuria and proteinuria attributed to IgA nephropathy,S3-S5 thin basement membrane nephropathy,S6 or hypertension.S1,S4,S7 In several cases, AS was only diagnosed after a progressive decline in kidney function prompted clinical re-evaluation.S1,S3,S5 Some patients were already at CKD stage III–V when AS was confirmed.S1,S7 Majority of the publications involved heterozygous COL4A3 or COL4A4 variants, consistent with autosomal dominant AS.S1-S8 There were also reports of hypomorphic COL4A5 X-linked variants, which occurred in older females with milder AS disease trajectories.S11 Extrarenal disease features varied considerably – in one case, sensorineural hearing loss preceded AS diagnosis by almost a decade,S1 whereas in other cases, sensorineural hearing loss was absent or indistinguishable from age-related changes.S2,S5,S7,S9 Kidney biopsy findings were also heterogeneous, whilst some reports demonstrated characteristic glomerular basement membrane lamellation, others showed only basement membrane thinning or non-specific changes.S2,S3,S7 Nevertheless, in nearly all cases, genetic confirmation (rather than histology alone) established the AS diagnosis and facilitated cascade screening in patient relatives.S1-S5,S7-S9
Considered together, these reports demonstrate that AS may remain undetected well into later adulthood and should be considered in older individuals with persistent haematuria, proteinuria, or unexplained CKD, even in the absence of classic AS features. Earlier recognition and broader use of genetic testing may prevent diagnostic delay, guide management, and support family screening.
Conflicts of interest
There are no conflicts of interest.